Page 196 - 2014 Printable Abstract Book
P. 196
of metabolic reprogramming. T cell subset results shed light on the effects of radiation on different T cell
subsets and the relevant signaling pathways mediating these effects. The current study indicates that our
metabolomics platform and the T cell subset differentiation methods are useful and informative
approaches for investigation and assessment of immune cell function after radiation. The mechanistic
findings on metabolic pathways may help to identify potential targets for intervention.
(PS3-11) Involvement of IL-8 in radiation-induced, atherosclerosis-related adhesiveness changes of
1
1
1
arterial endothelium. Stephen K. Babitz, M.S. ; Chad W. Dunaway, M.S. ; Chad Steele, PhD ; Dennis F.
1;2
1
Kucik University of Alabama at Birimingham, Birmingham, AL and Birmingham Veterans Affairs Medical
2
Center, Birmingham, AL
Epidemiological evidence indicates that terrestrial radiation, whether from cancer therapy,
atomic bombs, or excess occupational exposure, is a risk factor for cardiovascular disease. Although
heavy-ion radiation, such as that astronauts will encounter on a Mars mission, interacts very differently
with tissues than the high-energy photons most commonly encountered on Earth, we showed earlier that
x-rays, 56Fe, and 28Si all accelerate atherogenesis in the apoE -/- mouse model. The current strategy to
minimize risk from terrestrial radiation sources is to limit exposure. For astronauts on deep space
missions, however, exposure to a significant amount of radiation will be unavoidable. Therefore, an
understanding of the mechanism of radiation-induced atherosclerosis will be essential in order to develop
countermeasures. An early, atherogenic event is increased adhesiveness of vascular endothelium, leading
to inappropriate accumulation of monocytes, which can initiate a self-perpetuating inflammatory
response. Arterial inflammation, in turn, can contribute to development of clinically significant
atherosclerosis. We have shown that both x-rays and heavy ions increase adhesion of monocytic cells to
human aortic endothelial cells (HAECs) in vitro under conditions that mimic the shear stress in the
bloodstream. These adhesiveness changes can occur even without changes in adhesion molecule
expression levels, but do require chemokine-mediated signaling. Here we identify IL-8 as the specific
endothelial chemokine responsible for this effect. X-irradiation increased IL-8 secretion almost 5-fold,
while having little or no effect on expression of 15 other atherosclerosis-related chemokines. Radiation-
induced endothelial adhesiveness was specifically blocked by anti-IL-8 antibody, with no effect on
baseline, radiation-independent adhesion. Recombinant human IL-8 added to un-irradiated HAECs
increased adhesion to the same level as x-rays. Therefore, radiation-induced IL-8 signaling is both
necessary and sufficient for radiation-induced endothelial adhesiveness. This may explain, at least in part,
the mechanism by which radiation accelerates development of atherosclerosis. A better understanding of
this mechanism can provide the basis for future countermeasure development.
(PS3-12) Long-term differential changes in mouse intestinal metabolomics after γ and heavy ion
radiation exposure. Amrita K. Cheema, PhD; Shubhankar Suman, PhD; Prabhjit Kaur, PhD; Rajbir Singh,
PhD; Albert J. Fornace Jr., MD; Kamal Datta, MD. Department of Biochemistry and Molecular & Cellular
Biology, Georgetown University, Washington, DC
Tissue consequences of radiation exposure are dependent on radiation quality and high linear
energy transfer (high-LET) radiation, such as heavy ions in space is known to deposit higher energy in
tissues and cause greater damage than low-LET γ radiation. While radiation exposure has been linked to
194 | P a g e
subsets and the relevant signaling pathways mediating these effects. The current study indicates that our
metabolomics platform and the T cell subset differentiation methods are useful and informative
approaches for investigation and assessment of immune cell function after radiation. The mechanistic
findings on metabolic pathways may help to identify potential targets for intervention.
(PS3-11) Involvement of IL-8 in radiation-induced, atherosclerosis-related adhesiveness changes of
1
1
1
arterial endothelium. Stephen K. Babitz, M.S. ; Chad W. Dunaway, M.S. ; Chad Steele, PhD ; Dennis F.
1;2
1
Kucik University of Alabama at Birimingham, Birmingham, AL and Birmingham Veterans Affairs Medical
2
Center, Birmingham, AL
Epidemiological evidence indicates that terrestrial radiation, whether from cancer therapy,
atomic bombs, or excess occupational exposure, is a risk factor for cardiovascular disease. Although
heavy-ion radiation, such as that astronauts will encounter on a Mars mission, interacts very differently
with tissues than the high-energy photons most commonly encountered on Earth, we showed earlier that
x-rays, 56Fe, and 28Si all accelerate atherogenesis in the apoE -/- mouse model. The current strategy to
minimize risk from terrestrial radiation sources is to limit exposure. For astronauts on deep space
missions, however, exposure to a significant amount of radiation will be unavoidable. Therefore, an
understanding of the mechanism of radiation-induced atherosclerosis will be essential in order to develop
countermeasures. An early, atherogenic event is increased adhesiveness of vascular endothelium, leading
to inappropriate accumulation of monocytes, which can initiate a self-perpetuating inflammatory
response. Arterial inflammation, in turn, can contribute to development of clinically significant
atherosclerosis. We have shown that both x-rays and heavy ions increase adhesion of monocytic cells to
human aortic endothelial cells (HAECs) in vitro under conditions that mimic the shear stress in the
bloodstream. These adhesiveness changes can occur even without changes in adhesion molecule
expression levels, but do require chemokine-mediated signaling. Here we identify IL-8 as the specific
endothelial chemokine responsible for this effect. X-irradiation increased IL-8 secretion almost 5-fold,
while having little or no effect on expression of 15 other atherosclerosis-related chemokines. Radiation-
induced endothelial adhesiveness was specifically blocked by anti-IL-8 antibody, with no effect on
baseline, radiation-independent adhesion. Recombinant human IL-8 added to un-irradiated HAECs
increased adhesion to the same level as x-rays. Therefore, radiation-induced IL-8 signaling is both
necessary and sufficient for radiation-induced endothelial adhesiveness. This may explain, at least in part,
the mechanism by which radiation accelerates development of atherosclerosis. A better understanding of
this mechanism can provide the basis for future countermeasure development.
(PS3-12) Long-term differential changes in mouse intestinal metabolomics after γ and heavy ion
radiation exposure. Amrita K. Cheema, PhD; Shubhankar Suman, PhD; Prabhjit Kaur, PhD; Rajbir Singh,
PhD; Albert J. Fornace Jr., MD; Kamal Datta, MD. Department of Biochemistry and Molecular & Cellular
Biology, Georgetown University, Washington, DC
Tissue consequences of radiation exposure are dependent on radiation quality and high linear
energy transfer (high-LET) radiation, such as heavy ions in space is known to deposit higher energy in
tissues and cause greater damage than low-LET γ radiation. While radiation exposure has been linked to
194 | P a g e
